Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion

• Published in: Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (49), p.19526-19531
• Main Authors: Wen Lin, Hung, Liu, Chao-Zong, Cao, Deshou, Chen, Po-Yi, Chen, Mei-Fang, Lin, Shinn-Zong, Mozayan, Mansoor, Chen, Alex F, Premkumar, Louis S, Torry, Donald S, Lee, Tony J.-F
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor; Animals; Bioassay; Biological Sciences; Blood flow; Cells, Cultured; Electric Stimulation; Enzyme Inhibitors - pharmacology; Esters; Fatty acids; Ganglia; Gene expression; Kinases; Male; Nervous system; Neurons; Neurotransmitters; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitroarginine - pharmacology; Oocytes - physiology; Oxides; Palmitates - metabolism; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - metabolism; Stearic Acids - metabolism; Superior cervical ganglion; Superior Cervical Ganglion - cytology; Superior Cervical Ganglion - drug effects; Superior Cervical Ganglion - metabolism; Sympathectomy; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tissues; Vasodilation; Vasodilation - physiology; Vasodilators; Xenopus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0810262105

Nitric oxide (NO) is identified as the endothelium-derived relaxing factor and a neurotransmitter with a superfusion bioassay cascade technique. By using a similar technique with rat superior cervical ganglion (SCG) as donor tissue and rabbit endothelium-denuded aortic ring as detector tissue, we report here that a vasodilator, which is more potent than NO, is released in the SCG upon field electrical stimulation (FES) or addition of nicotine. Release of this vasodilator was enhanced by arginine analogs, including Nω-nitro-L-arginine (a NO synthase inhibitor), suggesting that it is not NO. Analysis by gas chromatography/mass spectrometry identified 2 saturated fatty acids, palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME), being released from the SCG upon FES in the presence of arginine analogs. Exogenous PAME but not SAME induced significant aortic dilation (EC₅₀ = 0.19 nM), indicating that PAME is the potent vasodilator. Release of PAME and SAME was significantly diminished in chronically decentralized SCG but not denervated SCG, suggesting the preganglionic origin. Furthermore, release of both fatty acids was calcium- and myosin light chain kinase-dependent, suggesting that both were released from axoplasmic vesicular stores. Electrophysiological studies further demonstrated that PAME but not SAME inhibited nicotine-induced inward currents in cultured SCG and the α7-nicotinic acetylcholine receptor-expressing Xenopus oocytes. Endogenous PAME appears to play a role in modulation of the autonomic ganglionic transmission and to complement the vasodilator effect of NO.